[unreadable] This research proposal is focusing on the development of ultrasound imaging methods to detect and characterize in vivo blood flow rheological disorders attributed to red blood cell (RBC) hyper-aggregation. It is known that the intensity of the ultrasound signal backscattered by blood is modulated by RBC aggregation. Theoretical models have further established the link between the ultrasound signal power and the volume of aggregates. In human and animal blood vessels, the aggregation and disaggregation of RBC aggregates are dynamically modulated by the flow condition, and the existence of pathologies affecting the protein content of the plasma. The rheological impacts of RBC aggregation in mammalian physiology are numerous and involve both the macro- and microcirculation. Among them may be cited its effect on the formation of sludge blood in microvessels, increased blood viscosity, occurrence of vascular thrombosis, and increased flow resistance. The ability of blood to perform its main function, i.e. to transport oxygen, carbon dioxide, nutrients and metabolic products can be affected by abnormally high levels of RBC aggregation. It is hypothesized that ultrasound can provide a tool to non-invasively measure RBC aggregation and blood flow disorders. The specific objectives are: 1) To measure, by ultrasonic means, the structural changes in RBC aggregation induced by copolymer coating, in either rat or mouse models; 2) To measure, by ultrasonic means, the endothelial vasoactive response following injection of vasoactive agents, 3) To measure, by ultrasonic means, the peripheral blood flow resistance in mouse models of sickle cell anemia and b-thalassemia, 4) To measure, by ultrasonic means, RBC perfusion disorders with an ultrasonic contrast agent, and 5) To follow-up the success of genetic therapies for sickle cell anemia and b-thalassemia by measuring either the RBC aggregation level with ultrasound, the endothelial vasoactive response with ultrasound, the peripheral blood flow resistance with ultrasound, and/or the RBC tissue perfusion disorders with an ultrasound contrast agent. [unreadable] [unreadable] [unreadable]